scholarly journals Sjogren’s Syndrome and TAM Receptors: A Possible Contribution to Disease Onset

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Richard Witas ◽  
Ammon B. Peck ◽  
Julian L. Ambrus ◽  
Cuong Q. Nguyen
Keyword(s):  
Autoimmune Disease ◽  
Sjögren’S Syndrome ◽  
Lupus Erythematosus ◽  
Sjögren's Syndrome ◽  
Disease Onset ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Type I ◽  
Apoptotic Cells ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome (SS) is a chronic, progressive autoimmune disease featuring both organ-specific and systemic manifestations, the most frequent being dry mouth and dry eyes resulting from lymphocytic infiltration into the salivary and lacrimal glands. Like the related autoimmune disease systemic lupus erythematosus (SLE), SS patients and mouse models display accumulation of apoptotic cells and a Type I interferon (IFN) signature. Receptor tyrosine kinases (RTKs) of the Tyro3, Axl, and Mer (TAM) family are present on the surface of macrophages and dendritic cells and participate in phagocytosis of apoptotic cells (efferocytosis) and inhibition of Type I IFN signaling. This review examines the relationship between TAM receptor dysfunction and SS and explores the potential contributions of TAM defects on macrophages to SS development.

scholarly journals Current Concepts: Mouse Models of Sjögren's Syndrome

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Tegan N. Lavoie ◽  
Byung Ha Lee ◽  
Cuong Q. Nguyen
Keyword(s):  
Autoimmune Disease ◽  
Sjögren’S Syndrome ◽  
Mouse Models ◽  
Lupus Erythematosus ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Unknown Etiology ◽  
Biliary Cirrhosis ◽  
Sjögren‘S Syndrome

Sjögren's syndrome (SjS) is a complex chronic autoimmune disease of unknown etiology which primarily targets the exocrine glands, resulting in eventual loss of secretory function. The disease can present as either primary SjS or secondary SjS, the latter of which occurs concomitantly with another autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or primary biliary cirrhosis. Current advancements in therapeutic prevention and treatment for SjS are impeded by lack of understanding in the pathophysiological and clinical progression of the disease. Development of appropriate mouse models for both primary and secondary SjS is needed in order to advance knowledge of this disease. This paper details important features, advantages, and pitfalls of current animal models of SjS, including spontaneous, transgenic, knockout, immunization, and transplantation chimera mouse models, and emphasizes the need for a better model in representing the human SjS phenotype.

scholarly journals Defective Efferocytosis in a Murine Model of Sjögren’s Syndrome Is Mediated by Dysfunctional Mer Tyrosine Kinase Receptor

2021 ◽  
Vol 22 (18) ◽  
pp. 9711
Author(s):  
Richard Witas ◽  
Astrid Rasmussen ◽  
Robert H. Scofield ◽  
Lida Radfar ◽  
Donald U. Stone ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Protective Role ◽  
Sjogren's Syndrome ◽  
Tyrosine Kinase Receptor ◽  
Apoptotic Cells ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SjS) is a chronic autoimmune disease primarily involving the exocrine glands in which the involvement of the innate immune system is largely uncharacterized. Mer signaling has been found to be protective in several autoimmune diseases but remains unstudied in SjS. Here, we investigated the role of Mer signaling in SjS. Mer knockout (MerKO) mice were examined for SjS disease criteria. SjS-susceptible (SjSS) C57BL/6.NOD-Aec1Aec2 mice were assessed for defective Mer signaling outcomes, soluble Mer (sMer) levels, A disintegrin and metalloprotease 17 (ADAM17) activity, and Rac1 activation. In addition, SjS patient plasma samples were evaluated for sMer levels via ELISA, and sMer levels were correlated to disease manifestations. MerKO mice developed submandibular gland (SMG) lymphocytic infiltrates, SMG apoptotic cells, anti-nuclear autoantibodies (ANA), and reduced saliva flow. Mer signaling outcomes were observed to be diminished in SjSS mice, as evidenced by reduced Rac1 activation in SjSS mice macrophages in response to apoptotic cells and impaired efferocytosis. Increased sMer was also detected in SjSS mouse sera, coinciding with higher ADAM17 activity, the enzyme responsible for cleavage and inactivation of Mer. sMer levels were elevated in patient plasma and positively correlated with focus scores, ocular staining scores, rheumatoid factors, and anti-Ro60 levels. Our data indicate that Mer plays a protective role in SjS, similar to other autoimmune diseases. Furthermore, we suggest a series of events where enhanced ADAM17 activity increases Mer inactivation and depresses Mer signaling, thus removing protection against the loss of self-tolerance and the onset of autoimmune disease in SjSS mice.

scholarly journals AB0609 THE SPECTRUM OF ANTINUCLEAR ANTIBODIES IN PATIENTS WITH SYSTEMIC SCLEROSIS POSITIVE FOR ANTI-U1RNP

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1600.1-1601
Author(s):  
R. Shayakhmetova ◽  
L. P. Ananyeva ◽  
O. Koneva ◽  
M. Starovoytova ◽  
O. Ovsyannikova ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Sjögren’S Syndrome ◽  
Lupus Erythematosus ◽  
Clinical Picture ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Normal Limits ◽  
Musculoskeletal Manifestations ◽  
Sjögren‘S Syndrome

Background:Patients with systemic sclerosis positive for anti-U1RNP have special clinical picture and disease progression. The autoimmune profile in this group is poorly understood.Objectives:The purpose of our work was to study the level of major autoantibodies in patients with systemic sclerosis positive for anti-U1RNP.Methods:The study included 80 patients (71 women and 9 men, mean age 44,5±14 years) positive for antibodies to RNP and meeting the criteria of the systemic sclerosis (ACR/EULAR 2013). Patients were examined for autoantibodies: RF, ACCP, ACA, anti-Scl70, anti-RNAP-III, anti-Ro, anti-La, anti-dsDNA, anti-Sm, ACL, anti-Jo1. 44 patients were examined in dynamics in 24 months.Results:In the study group the clinical picture was dominated by inflammatory musculoskeletal lesions (synovitis and myopathy), skin manifestations were poorly expressed. Interstitial lung disease was detected in 68% of cases. Overlaps (34%) with other rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus) and combination with Sjogren’s syndrome (32.5%) were frequently noted. Other antibodies were often detected: commonly - RF (31%), anti-Ro (38%), anti-dsDNA (42%), rarely - anti-Sm (11%), ACCP (8%), anti-La (8%), ACA (6%), anti-Scl70 (6%), AKL (2%). Anti-Jo1 and anti-RNAP-III were not detected at all. In patients with systemic sclerosis highly-positive for anti-U1RNP (more than 2 upper normal limits) RF, anti-Ro, anti-dsDNA were significantly more common in comparison with low-positive(p=0.00). In dynamics 80% of patients maintained anti-U1RNP, while other autoantibodies were detected with the same frequency. In patients with initially low titer of anti-U1RNP, their disappearance was noted.Conclusion:Patients with systemic sclerosis positive for anti-U1RNP differ in the predominance of inflammatory musculoskeletal manifestations and frequent combination with Sjogren’s syndrome and overlaps. Highly positivity for anti-U1RNP is accompanied by a persistent increase in RF, anti-Ro, anti-dsDNADisclosure of Interests:None declared

scholarly journals Doença Intersticial Pulmonar Grave e Mania Induzida por Corticosteróides em Doente com Lúpus Eritematoso Sistémico e Síndrome de Sjögren Secundária

2017 ◽  
Vol 30 (3) ◽  
pp. 246 ◽  
Author(s):  
Sofia Silvério Serra ◽  
Teresa Pedrosa ◽  
Sandra Falcão ◽  
Jaime Cunha Branco
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Sjögren’S Syndrome ◽  
Lupus Erythematosus ◽  
Sjögren's Syndrome ◽  
Manic Episode ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Neurological Involvement ◽  
Systemic Lupus ◽  
Sjögren‘S Syndrome

Interstitial lung disease occurs in up to 25% of patients with Sjögren’s syndrome and 2% - 8 % of patients with systemic lupus erythematosus. Corticosteroid therapy remains the main treatment for systemic lupus erythematosus. However, it can be associated with several neuropsychiatric disorders especially with prednisolone at a dose of more than 40 mg/day. We present the case of a 51-year-old patient with systemic lupus erythematosus and secondary Sjögren’s syndrome with severe pulmonary involvement four years after the diagnosis. Chest computed tomography revealed neofibrosis and ground glass appearance pattern. After increasing the dose of prednisolone to 60 mg/day, the patient presented a manic episode. There was need of hospitalization and the situation was considered to be secondary to corticosteroids at high doses. Central neurological involvement by organic disease was excluded.We introduced monthly perfusion of cyclophosphamide for six months and later started mycophenolate mofetil 2 g/day, reducing prednisolone to 10 mg/day and maintaining hydroxychloroquine 400 mg/day, with control of disease activity.

scholarly journals TLR7 Signaling Drives the Development of Sjögren’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Yawen Wang ◽  
Annie Roussel-Queval ◽  
Lionel Chasson ◽  
Noël Hanna Kazazian ◽  
Laetitia Marcadet ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Autoimmune Disease ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoantibody Production ◽  
Deficient Mice ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease that affects predominately salivary and lacrimal glands. SS can occur alone or in combination with another autoimmune disease like systemic lupus erythematosus (SLE). Here we report that TLR7 signaling drives the development of SS since TLR8-deficient (TLR8ko) mice that develop lupus due to increased TLR7 signaling by dendritic cells, also develop an age-dependent secondary pathology similar to associated SS. The SS phenotype in TLR8ko mice is manifested by sialadenitis, increased anti-SSA and anti-SSB autoantibody production, immune complex deposition and increased cytokine production in salivary glands, as well as lung inflammation. Moreover, ectopic lymphoid structures characterized by B/T aggregates, formation of high endothelial venules and the presence of dendritic cells are formed in the salivary glands of TLR8ko mice. Interestingly, all these phenotypes are abrogated in double TLR7/8-deficient mice, suggesting that the SS phenotype in TLR8-deficient mice is TLR7-dependent. In addition, evaluation of TLR7 and inflammatory markers in the salivary glands of primary SS patients revealed significantly increased TLR7 expression levels compared to healthy individuals, that were positively correlated to TNF, LT-α, CXCL13 and CXCR5 expression. These findings establish an important role of TLR7 signaling for local and systemic SS disease manifestations, and inhibition of such will likely have therapeutic value.

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